This proposal is to request support for a Keystone Symposia meeting entitled Computer-Aided Drug Design, organized by Michael K. Gilson, Catherine E. Peishoff and Jeff Blaney, which will be held in Whistler, British Columbia, and Canada from April 20 - 25, 2010. The purpose of this meeting is to stimulate progress in the methods of computer-aided drug design. The Keystone Symposia meeting on Computer-Aided Drug Design aims to advance the state of the art in affinity prediction by assembling scientists doing innovative work on the modeling and basic physics of protein-small molecule binding at the theoretical, computational and experimental levels. The meeting will furthermore challenge and stimulate the computational participants with the opportunities and practicalities of real-world drug discovery, and will provide a perspective of the need and potential for methods to address the downstream problems that lead to candidate attrition. This will be accomplished by bringing theory and practice into contact at a number of levels in order to highlight interesting and important practical problems waiting to be solved, and by deepening participants'understanding of the science underlying these challenges. Intensive contacts among scientists with a broad spectrum of interlinked interests will spark new collaborations and will motivate and catalyze advances in computer-aided drug discovery. Opportunities for interdisciplinary interactions will be significantly enhanced by the concurrent meeting on New Directions in Small Molecule Drug Discovery, which will share four sessions and a keynote with this meeting. PUBLIC HEALTH RELEVANCE: Small molecule drugs are a mainstay of modern therapeutics, as they are a central means of translating our growing understanding of the molecular mechanisms of disease into medications to improve and extend life. The aim of the Keystone Symposia meeting on Computer-Aided Drug Design is to stimulate progress in the methods of computer-aided drug design by bringing theory and practice into contact at a number of levels, highlighting interesting and important practical problems waiting to be solved and deepening participants'understanding of the underlying science.